| 8-month study |
Chronic (>90 days) |
The groups differed according to the distilled drinking water
concentrations of fluoride which was added as sodium fluoride. The
initial water fluoride concentrations were 0, 10.0, 25.0 and 50.0 mg/L.
The rats were provided with a chemically defined, low-fluoride diet
(0.4 mg/kg, American Institute of Nutrition Diet AIN-76A) throughout
the eight-month study.
At the end of each of the first four weeks the rats were weighed
and the 48-h water intakes were measured gravimetrically. Based on
the volume of water consumed and the change in body weight of each
group during the week, the water fluoride concentrations were
increased in order to maintain a relatively constant daily dose of
fluoride. The target doses were 3.0, 6.0 and 12.0 mg F/kg body wt/day.
Compared to using fixed water fluoride concentrations, this method
substantially increases the exposure levels, thus increasing the
likelihood of detecting adverse effects. Such adjustments were made
each week during the first month, biweekly during the second month
and once each month for the remainder of the study when rates of
change in body weight were relatively small. During the last month of
the study the drinking water fluoride concentrations were 33.2, 85.6
and 155.2 mg/L. Considering the entire eight-month study, the
average daily doses for the three fluoride groups were 2.9, 5.7 and
11.5 mg F/kg/day. Fluoride intake from the foodwas a small fraction of
that from water (b0.01 mg F/kg/day).; The protocol for the study was reviewed and approved by the
Institutional Animal Use and Care Committees of the Medical College
of Georgia and Augusta State University. Female Sprague–Dawley rats
(n=32) were received one week after weaning, an age at which all
regions of the central nervous system are rapidly developing. They
were placed in pairs in ‘shoebox’ cages, numbered with indelible ink on
their tails, weighed and randomly assigned to four groups (8/group). |